Genital herpes is a major health problem in the U.S. The prevalence of these infections is dramatically increasing despite effective antiviral drugs. This increase puts young adults and infants at risk of genital and neonatal herpes, respectively. Neonatal herpes infections are associated with neurologic impairment and high mortality. In addition, active genital herpes lesions facilitate the transmission of HIV. Much of the transmission is due to asymptomatic shedding which highlights the need for an efficacious prophylactic vaccine to reduce the spread of genital herpes and thereby reduce the incidence of neonatal herpes. A recent Institute of Medicine report on vaccine priorities for 21st century highlights the need for a safe and effective vaccine for genital herpes. Aviron proposes to develop a live attenuated vaccine to prevent HSV-2 disease. A live, attenuated, recombinant HSV-2 virus lacking both copies of gamma1 34.5 gene in addition to UL55, UL56, and US10-US12 was constructed. This recombinant was highly neuroattenuated and genetically stable. During this proposal this virus will be evaluated in the guinea pig model of genital herpes for safety and efficacy. In addition further in vitro characterization will enable high quality clinical trial material to be produced for IND enabling primate studies and early Phase I human trials. PROPOSED COMMERCIAL APPLICATION: Not Available